Pain is the common symptom of most of the diseases and it is a kind of unpleasant feeling with large individual difference in human. Since pain causes tremendous suffering to people, the 106th national congress of USA has passed a resolution and declared the ten years since Jan. 1, 2001 as the Decade of Pain Control and Research according to the report on Volume 2 of “Newsletter of the International Association for the Study Pain” in 2001. Therefore, it can be found that various countries have placed emphasis on the pain research. According to the time course of pain, it can be divided into acute pain (physiological pain) and chronic pain (pathological pain). Wherein, chronic pain includes inflammatory pain, neuropathic pain and cancer pain, which is one of the frequently seen chief complaints in clinical study. Since the mechanism of chronic pain is complex, its treatment has become a difficult problem in clinical study. Neuropathic pain refers to the pain syndrome that is induced by injuries in nervous system or diseases, which is always characterized by spontaneous pain, hyperpathia to mechanical stimulation, cold, heat and other harmful stimulation; allodynia, paralgesia, burn pain and other nervous pathological hyperpathia to non-harmful stimulation. Since the duration of chronic pain is always long and causes relatively big damages to physical and mental health of people, the studies on this topic have become the hot spot and emphasis of pain field. Burn is a kind of serious wound and burn pain is also one of the most serious acute pain, and inflammatory pain may be induced by inflammatory reactions after burn. Pain is often the first reaction of burn patients, different degrees of pain may be found in the wound surface or no significant pain is found at the first hour after burn, and subsequent pain is always affected by the following factors: such as depth of burn, stage for course of disease, therapeutic measures, individual factors of patients and so on. Pain after burn is induced by the stimulation to nociceptor on the skin of injured portion as well as accompanied inflammatory reactions and nerve injuries, therefore, its treatment requires the combination of nociceptive treatment and neuropathic treatment.
Purine adenosine triphosphate (ATP) is involved in pain information transmission as an important messenger substance. Purine receptors can be divided into Purine 1 and Purine 2 (P1,P2) receptor, ATP and its analogs can take effects on P2 receptor. P2 receptor can be divided into ligand gated ion channel receptor (P2X receptor) and G protein coupled receptor (P2Y receptor). P2X receptor has seven kinds of subtypes (P2X1-7). It was reported in Nature of the United Kingdom that P2X3 receptor (a subtype of P2X receptor) that reacted with ATP can be specifically cloned and expressed in the neurons in dorsal root ganglion. Pain and noxious stimulation can lead to the release of ATP in large amount by injured cells, stress cells and sensory nerve ending itself. ATP and reactive P2X receptor are involved in the transmission of pain and noxious information in primary sensory neurons, among them homologously polymerized P2X3 receptor is involved in the transmission of pain and noxious information in primary sensory neurons. P2X3 receptor gene knock-out mice reduced the two-phase reaction in formalin pain inducing experiment. P2X3 receptor can mediate the transmission of pain in neuropathic pain. The expression of P2X3 receptor and P2X3mRNA increases during the stimulation in neuropathic pain, sensory neuron P2X3 receptor-mediated ATP-activated electric current via gated channel significant increases. Application of P2X3 receptor anti-sense oligonucleotide and RNA interference technique may down-regulate the level of P2X3 receptor in the dorsal root ganglion of inflammatory pain model of rats, and then significantly alleviate the noxious reaction in footplates that are induced by P2X3 receptor agonist α,β-meATP and formalin. These findings can provide new evidences for the pathogenesis of neuropathic pain. Previous studies in the laboratory by the applicant have also indicated that burn may lead to the increase in P2X3 receptor expression in the sensory neurons of dorsal root ganglion. Currently, studies have been reported on preparation of P2X3 receptor antagonists (such as RO3) for clinical treatment on pain in other countries.
Pain relieved by chemical drugs is still the most frequently used therapeutic tool on pain now, which mainly includes opioid analgesic, non-opioid analgesic with central effect, anti-inflammatory analgesic with peripheral effect and compound anti-inflammatory analgesic. But the incidence rate of adverse effects such as respiratory depression, nausea, vomit, drowsiness, urinary retention and other symptoms in opioid and other analgesic is relatively high, and long-term application may lead to drug tolerance and dependence as well as withdrawal syndrome that is induced by sudden drug withdrawal. Antifani (Indometacin) is a kind of non-steroid anti-inflammatory drug having antipyretic effects, abirritation and anti-inflammatory effect, and its mechanism is to reduce prostaglandin synthesis by inhibiting epoxidase, prevent the formation of pain nerve impulse in inflammatory tissues and inhibit inflammatory reactions, including chemotropism of leucocytes, release of lysomal enzymes and so on. Since idomethine has several kinds of serious adverse effects, its applicable range is thus affected. Therefore, the exploration of analgesic drug on the basis of new molecular targets has become the hot spot of researches and the most important task now.
Puerarin is a kind of flavonoid glycoside that is extracted from the root of leguminous plant Pueraria lobata and Pueraria thomsonii Benth., which is mainly used in the treatment on cardiovascular diseases and diabetes. Previous studies have reported that [Zhou Jun, Fang Suping, Qi Yun, et al. Effect of GeGen Decoction on Inflammatory Media in Joint of Adjuvant Arthritis Rats. Chinese Journal of Experimental Traditional Medical Formulae, 2001, 7(3): 29-31.] Puerariae Decoction with pueraria as the major drug has anti-inflammatory action. This study indicates that puerarin that is extracted from pueraria may prevent noxious reactions and affect pain sense, but no result on the direct abirritation of puerarin has been reported, and no report on the treatment on pain by utilizing analgesic effects of puerarin is available in clinical study.